Trifluoroacetic acid → HCID 71582309, compound

HRID 2359140Notes

Reaction equation

HRID 2359140 reaction equation
FC(F)(F)C(O)=O.[Cl:8][C:9]1[CH:14]=[C:13]([Cl:15])[CH:12]=[CH:11][C:10]=1[C@H:16]([N:18]1[C:26]2[C:21](=[CH:22][CH:23]=[C:24]([N:27]3[CH2:32][CH2:31][N:30]([C:33]([C@H:35]4[CH2:39][CH2:38][CH2:37][N:36]4C(OC(C)(C)C)=O)=[O:34])[C@H:29]([CH2:47][OH:48])[CH2:28]3)[CH:25]=2)[CH:20]=[N:19]1)[CH3:17]>ClCCl>[Cl:8][C:9]1[CH:14]=[C:13]([Cl:15])[CH:12]=[CH:11][C:10]=1[C@H:16]([N:18]1[C:26]2[C:21](=[CH:22][CH:23]=[C:24]([N:27]3[CH2:32][CH2:31][N:30]([C:33]([C@H:35]4[CH2:39][CH2:38][CH2:37][NH:36]4)=[O:34])[C@H:29]([CH2:47][OH:48])[CH2:28]3)[CH:25]=2)[CH:20]=[N:19]1)[CH3:17]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86688453HCID 86688453, compound

Product 1

HCID 71582309HCID 71582309, compoundYield 20%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (0.5 mL) was added to a solution of (R)-t-butyl 2-((S)-4-(1-((R)-1-(2,4-dichlorophenyl)ethyl)-1H-indazol-6-yl)-2-(hydroxymethyl)piperazine-1-carbonyl)pyrrolidine-1-carboxylate (0.072 g, 0.12 mol) in dichloromethane (2 mL) and the mixture was stirred at room temperature for 30 min. Excess solvent was removed in vacuo, and the residue was diluted with dichloromethane (15 mL). The organic layer was neutralized with saturated aqueous sodium bicarbonate, and the aqueous layer was further extracted with dichloromethane (2×15 mL). The combined organic layers were dried (Na2SO4), filtered, and concentrated in vacuo. The crude product was purified by flash chromatography (SiO2, 0-30% methanol in dichloromethane) to give the title compound as a white solid (0.012, 0.024 mol, 20%). 1H NMR (400 MHz, CDCl3) δ 7.92 (s, 1 H), 7.56 (d, J=8.4 Hz, 1 H), 7.37 (d, J=2.0 Hz, 1 H), 7.18-7.09 (m, 2 H), 6.80 (d, J=7.6 Hz, 1 H), 6.60 (s, 1 H), 6.09 (q, J=6.8 Hz, 1 H), 4.82-4.78 (m, 2 H), 4.64-4.60 (m, 1 H), 4.12-4.07 (m, 2 H), 3.76-3.58 (m, 4 H), 3.43-3.38 (m, 2 H), 2.90-2.76 (m, 2 H), 2.48-2.36 (m, 1 H), 2.13-2.20 (m, 3 H), 1.98 (d, J=6.8 Hz, 3 H); MS: (ES) m/z calculated for C25H30Cl2N5O2 [M+H]+ 502.2, found 502.4.

Workup

  1. customExcess solvent was removed in vacuo
  2. additionthe residue was diluted with dichloromethane (15 mL)
  3. extractionthe aqueous layer was further extracted with dichloromethane (2×15 mL)
  4. dry with materialThe combined organic layers were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by flash chromatography (SiO2, 0-30% methanol in dichloromethane)

Sources & evidence

ORD record
ord-582f5aa1d84b4c59954e8853eb2324ce
Source dataset
uspto-grants-2014_04
Patent number
US08685959B2

Reaction notes

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